Associations of sphingosine-1-phosphate with thyroid function and structure: A cross-sectional population-based study.

OBJECTIVE: Sphingosine-1-phosphate (S1P) is a versatile immunomodulatory lipid mediator that affects both immune and cardiovascular health. S1P has been linked to thyroid health, for example, by affecting inflammatory reactions found in Graves' disease. In our study, we explored associations of S1P with thyroid markers obtained from laboratory tests (thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)) and ultrasound examination. METHODS: We quantified S1P by LC-MS/MS in participants from the population-based 'Study of Health in Pomerania' conducted in Northeast Germany. Serum levels of TSH, fT3, and fT4 were measured using chemiluminescent immunoassays. Thyroid volume, thyroid nodules, and echogenic patterns were assessed by ultrasonography. Cross-sectional associations between serum S1P and thyroid biomarkers were evaluated using multivariable linear regression models adjusted for confounding. RESULTS: The total study population consisted of 4,034 participants (51.6% women aged 20-84 years). A 1 μmol/L higher S1P level was associated with a 0.17 mIU/L lower TSH level (95% confidence interval (CI): -0.32; -0.04) and a 0.52 pmol/L (0.42; 0.63) higher fT3 level. These associations persisted after excluding individuals with high or low serum TSH levels and those taking thyroid medication. S1P levels were not significantly associated with serum fT4 levels. Higher S1P levels were associated with a larger thyroid volume, the presence of thyroid nodules, and a hypoechogenic thyroid pattern. CONCLUSION: Circulating S1P is inversely associated with TSH and positively associated with fT3, suggesting a potential modulatory role of S1P in thyroid function.